The present invention relates to a method for reducing or maintaining intraocular pressure. More particularly, it relates to a method for reducing or maintaining intraocular pressure involving the administration of an effective amount of a (2-imidazolin-2-ylamino) quinoxaline and/or a salt thereof, e.g., in an ophthalmically acceptable carrier.
The method of the present invention is particularly useful for the management of glaucoma, a disease of the eye characterized by increased intraocular pressure. On the basis of its etiology, glaucoma has been classified as primary or secondary. For example, primary glaucoma in adults may be either chronic open-angle or acute or chronic angle-closure. Secondary glaucoma results from pre-existing ocular diseases such as uveitis, intraocular tumor or an enlarged cataract.
The underlying causes of primary glaucoma are not yet well known. The increased intraocular pressure is due to obstruction of aqueous humor outflow. In chronic open-angle glaucoma, the anterior chamber and its anatomic structures appear normal, but drainage of the aqueous humor is impeded. In acute and chronic angle-closure glaucoma, the anterior chamber is shallow, the filtration angle is narrowed and the iris may obstruct the trabecular meshwork at the entrance to the canal of Schlemm. Dilation of the pupil may push the root of the iris forward against the angle or may produce pupillary block and thus precipitate an acute attack. Eyes with narrow anterior chamber angles are predisposed to acute angle-closure glaucoma attacks of varying degrees of severity.
Secondary glaucoma is caused by any interference with the flow of aqueous humor from the posterior chamber into the anterior chamber and, subsequently, into the canal of Schlemm. Inflammatory disease of the anterior segment may prevent aqueous escape by causing complete posterior synechia in iris bombe, and may plug the drainage channel with exudates. Other common causes are intraocular tumors, enlarged cataracts, central retinal vein occlusion, trauma to the eye, operative procedures and intraocular hemorrhage.
Considering all types together, glaucoma occurs in about 2% of all persons over the age of 40 and may be asymptomatic for years before progressing to rapid loss of vision. In cases where surgery is not indicated, topical beta-adrenoceptor antagonists have traditionally been the drugs of choice for treating glaucoma.
Various quinoxaline derivatives have been suggested as therapeutic agents. For example, Danielewicz, et al U.S. Pat. No. 3,890,319 discloses compounds as regulators of the cardiovascular system which have the following formula: ##STR1## where the 2-imidazolin-2-ylamino group may be in any of the 5-, 6-, 7- or 8- position of the quinoxaline nucleus; X, Y and Z may be in any of the remaining 5-, 6-, 7- or 8- positions and may be selected from hydrogen, halogen, lower alkyl, lower alkoxy or trifluoromethyl; and R is an optional substituent in either tho 2- or 3- position of the quinoxaline nucleus and may be hydrogen, lower alkyl or lower alkoxy. There is no suggestion in the Daniolewicz, et al patent that such compounds are useful in reducing or maintaining intraocular pressure.
In "Ocular effects of a relatively selective alpha 2 agonist (UK-14, 304-18) in cats, rabbits and monkeys", by J.A. Burke et al, Current Eye Research, Vol. 5, Nov. 9, 1986, the quinoxaline derivative ##STR2## was shown to be effective to reduce intraocular pressure in rabbits, cats and monkeys. No other quinoxaline derivatives were suggested as being useful to reduce intraocular pressure.